This is not the first time Kyrgios has been booed off the court in the United States, with the Australian also hit by a torrent of abuse in last year's Washington Open when he retired down 0-3 to American Tennys Sandgren.
Norrie, world No 73, won the first set 7-5 before the Australian pulled out after struggling with what appeared to be a recurring hip injury.
"Sorry Atlanta, Never the way I wanna go out, but gotta get my body right", he wrote on Instagram on Sunday.
At times Kyrgios seemed disinterested in the contest, with his effort in question late in the opening set before he meekly double-faulted to give Norrie the early break in the second.
"I have played really, really well all week".
Ebden is through to his second tour-level semi-final of the year as he strives for his maiden ATP title.
Isner now leads Ebden 4-1 in their head-to-head records after avenging his lone loss against the Aussie.
"I am definitely playing better than I was in the beginning of the year". He is also the only one in the group to ever win a tournament on the Tour - a pair of titles at Hamburg, including a year ago. He had the home crowd on his side.
Second-seeded Roberto Bautista Agut of Spain made quick work of Japan's Taro Daniel, winning 7-5, 6-1 on the clay to advance to the semifinals. "We have both played good tennis all week".